Background: Treatment of advanced unresectable hepatocellular carcinoma (HCC) has advanced substantially in the past few years with the use of immunotherapy. The IMbrave 150 phase III study assessed the combined treatment of atezolizumab plus bevacizumab (atezobev) and has demonstrated better overall and progression-free survival compared with sorafenib. We aimed to assess the efficacy and toxicity of atezobev in real-world data. Methods: We reviewed the medical records of patients with a diagnosis of advanced HCC treated at the Sheba Medical Center between January 2020 and February 2023. Eligible patients were those treated with atezobev as first line systemic therapy. Adverse events were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Response assessment was performed according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Results: We identified 37 patients that were treated with atezobev, mean age of the study population was 70 (IQR 60-72), 19% were females (n = 7), median ECOG performance status was 1 (IQR 0-1.5) and HCC etiology was non-viral in 35% (n = 13) and viral (HBV/HCV) in 65% of patients (n = 24). Overall response rate (ORR) was 29.7% (n = 11), stable disease was noted in 27.0% (n = 10) and progressive disease in 43.2% (n = 16) of patients. In comparison, the ORR reported in the IMbrave 150 study was 27%. There was no difference in response rate according to previous local treatment or HCC etiology. Grade 3/4 adverse events included grade 3 hepatitis (10.8%, n = 4), grade 3 diarrhea (2.7%, n = 1), and grade 4 infusion-related reaction (2.7%, n = 1). In comparison, the IMbrave 150 study reported grade 3/4 hepatitis, diarrhea, and infusion-related reaction in 7.0%, 1.8% and 2.4% of patients, respectively. Conclusions: In this cohort of advanced HCC patients treated in a large tertiary medical center, the efficacy and toxicity profile of atezobev was similar to that reported in the IMbrave 150 phase III study.